National Human Genome Research Institute

Bethesda, United States

National Human Genome Research Institute

Bethesda, United States

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News Article | May 17, 2017

An international team of researchers, led by University of New Mexico Associate Professor Coenraad Adema, is now one step closer to eliminating a deadly parasitic disease responsible for killing hundreds of thousands of people around the world every year. The research article, 'Whole genome analysis of a schistosomiasis-transmitting freshwater snail', published in Nature Communications this week, gives the scientific community an in-depth look of the sequenced genome of Biomphalaria glabrata, a tropical Ram's Horn snail. "Sequencing and characterizing the genome of this snail has given us a lot of information into its biology," said Adema, who is also part of UNM's Center for Evolutionary and Theoretical Immunology (CETI) that has played a pivotal role in this project. "It has informed us on animal evolution and supports the drive to minimize the impact of infectious disease on global health." This snail, which lives only in tropical climates, plays a significant role in the lifecycle of a parasitic disease called schistosomiasis, also known as snail fever or bilharzia. The parasite infects the snail early on its life, essentially taking over the snail's body, impacting its reproductive and metabolic processes. Once fully developed, the parasite leaves the snail, later infecting a human host through contact in water. According to Adema, if researchers can better understand how the snail/parasite interaction works, they may be able to stop it altogether, cutting the snail out of the parasite's lifecycle. And, because the snail is a critical part of the organism's development; without it, the parasite cannot fully mature and infect humans. Understanding the animal's genetic makeup is a critical component in being able to understand these interactions - something that is now possible thanks to this international team of researchers and support from the National Human Genome Research Institute of NIH for the sequencing effort. "Understanding the snail's genome gives us many avenues to cut the snail out of this parasite's lifecycle," Adema said. "Which one day may lead to the elimination of this disease." Schistosomiasis is a chronic parasitic disease. According to the World Health Organization (WHO), more than 66 million people were reported to have been treated for the disease in 2015, with another 218 million people requiring preventative treatment. On top of that, nearly a quarter of a million people die from snail fever every year, just in sub-Saharan Africa. The disease is also extremely easy to contract, which is part of the reason why it impacts so many people. Once the parasite leaves its host snail, it's able live in a body of water before breaking through skin to infect a human body. In Africa for example, simply putting your hand in the Nile River can lead to infection. The WHO hopes to eliminate snail fever by 2025 - a goal that is made increasingly more likely because of this investigation led by UNM. "After malaria, this is the worst parasitic disease on the planet," said Adema. "So, being able to do work that may help improve global human health outcomes it is a very important motivation for my research." More than 100 researchers from 50 institutions around the world are a part of this study and latest publication - a testament to how significant and wide-reaching this disease and its overall impact is. The international expertise in parasitology and invertebrate biology at UNM is underscored by important contributions of nearly a dozen different faculty, graduate students and research scientists from the Biology Department that are also part of this effort. Adema says several of his international colleagues are already exploring new, different ways to use the snail's genome to fight the disease. And while the parasite and corresponding illness are the main target of this research, there is also much more to learn from the genome. "This is an important contribution to better understanding infectious disease," he said. "It also gives us information on regulation of gene expression, comparative immunology, embryology, general biology of snails, animal evolution and many other things."

Talks and Papers Previewed at PMWC 2017 and SFAF Conferences Advance Nabsys' Mission to Democratize Structural Information PROVIDENCE, RI--(Marketwired - May 24, 2017) - Nabsys, a genomics company pioneering high-definition mapping of genomes using high-resolution, high-speed nanodetectors, today shared performance of its new electronic HD-Mapping™ platform and its ability to identify structural variation in both microbial and human genomes. The company also confirmed it is preparing for a beta program. In a talk titled "Whole Genome Mapping...Now in HD," Nabsys founder and CEO Dr. Barrett Bready revealed the advantages of using solid-state nanodetectors to build high-definition whole genome maps and analyze genomic structural variation (genomic changes larger than ~100 base pairs). He explained that despite advances in next generation sequencing technologies, limitations imposed by short read lengths of leading sequencing technologies combined with the repetitive nature of genomes present challenges for genome assembly and analysis. Longer range techniques such as optical mapping provide information over a larger scale, but lack resolution. "Nabsys' significant progress this past year puts us in a strong position to launch a beta program to select labs early next year with a full commercial launch to follow," Dr. Bready said. "By avoiding optics and going completely electronic and semiconductor-based, the platform will enjoy more than an order of magnitude cost advantage over optical mapping for both the instrument and consumables. We want to democratize genomic structural variation. Our goal by next year is to enable individual researchers to do whole genome structural variation analysis on their samples at their own benchtops." At PMWC, Dr. Bready showed data from pre-published papers titled "High-Definition Electronic Genome Maps from Single Molecule Data" and "Automated Structural Variant Verification in Human Genomes using Single-Molecule Electronic DNA Mapping." The papers are available for download from the company's website. Dr. Bready's talk follows presentations entitled, "High Density Electronic Maps to Verify Structural Variations in Human Genomes" and "De Novo Assembly of High Density Electronic Maps Reveal Structural Diversity in Bordetella pertussis" (better known as whooping cough) at the 12th Annual Sequencing, Finishing, and Analysis in the Future Conference. Nabsys collaborated with researchers at the Centers for Disease Control and Prevention (CDC) to create highly accurate whole genome electronic maps of pathogenic strains of B. pertussis enabling a level of structural analysis unavailable to existing mapping technologies. The precision and accuracy of Nabsys HD-Mapping™ allowed for distinction between highly related strains and identified structural differences which may contribute to observed variation in virulence and vaccine avoidance characteristics among the strains. Nabsys HD-Mapping™ The Nabsys HD-Mapping platform works by adding sequence-specific tags to long DNA molecules. These molecules are then driven through the nanodetectors at high velocity using a combination of electrophoretic and hydrodynamic control. The detector reports the locations of the sequence-specific tags on the molecules. The information is then analyzed by the Nabsys suite of software tools and can be used for the following applications: About Nabsys Nabsys is a privately held company that develops semiconductor-based tools for better genomic analysis. The company has pioneered the technology of electronic high-definition mapping that is capable of analyzing entire genomes in very large fragments (100,000 bp and higher) traveling at high velocity (greater than 1 million base pairs per second). Nabsys was the first company to receive a "1000 Genome" award from the National Human Genome Research Institute of the National Institutes of Health for an electronic approach to DNA analysis. For more information, please visit or contact us at Stay connected with Nabsys on Twitter:

Belkaid Y.,U.S. National Institutes of Health | Segre J.A.,National Human Genome Research Institute
Science | Year: 2014

Human skin, the body's largest organ, functions as a physical barrier to bar the entry of foreign pathogens, while concomitantly providing a home to myriad commensals. Over a human's life span, keratinized skin cells, immune cells, and microbes all interact to integrate the processes of maintaining skin's physical and immune barrier under homeostatic healthy conditions and also under multiple stresses, such as wounding or infection. In this Review, we explore the intricate interactions of microbes and immune cells on the skin surface and within associated appendages to regulate this orchestrated maturation in the context of both host physiological changes and environmental challenges.

Manolio T.A.,National Human Genome Research Institute
New England Journal of Medicine | Year: 2010

Over the past 5 years, genomewide association studies have yielded a wealth of insight into genes and chromosomal loci that contribute to susceptibility to disease. This article, the second in the Genomic Medicine series, describes the design of these studies and considers the extent to which the data they provide are useful in predicting the risk of disease. Copyright © 2010 Massachusetts Medical Society.

Gao B.,National Human Genome Research Institute
Current Topics in Developmental Biology | Year: 2012

Planar cell polarity (PCP), a process controlling coordinated, uniformly polarized cellular behaviors in a field of cells, has been identified to be critically required for many fundamental developmental processes. However, a global directional cue that establishes PCP in a three-dimensional tissue or organ with respect to the body axes remains elusive. In vertebrate, while Wnt-secreted signaling molecules have been implicated in regulating PCP in a β-catenin-independent manner, whether they function permissively or act as a global cue to convey directional information is not clearly defined. In addition, the underlying molecular mechanism by which Wnt signal is transduced to core PCP proteins is largely unknown. In this chapter, I review the roles of Wnt signaling in regulating PCP during vertebrate development and update our knowledge of its regulatory mechanism. © 2012 Elsevier Inc.

Aksentijevich I.,National Human Genome Research Institute
Seminars in Immunopathology | Year: 2015

Autoinflammatory diseases are a genetically heterogeneous group of rheumatologic diseases that are driven by abnormal activation of the innate immune system. Patients present with recurrent episodes of systemic inflammation and a spectrumof organ-specific comorbidities. These diseases are mediated by the overproduction of various inflammatory cytokines, such as IL-1, IL-18, IL-6, TNFα, and type I interferon. Treatments with biologic agents that inhibit these cytokines have been very efficient in most patients. During the past 2 years, remarkable progress has been made in the identification of disease-associated genes owing mostly to new technologies. Next generation sequencing technologies (NGS) have become instrumental in finding single-gene defects in undiagnosed patients with early onset symptoms. NGS has advanced the field of autoinflammation by identifying disease-causing genes that point to pathways not known to regulate cytokine signaling or inflammation. They include a protein that has a role in differentiation of myeloid cells, a ubiquitously expressed enzyme that catalyzes the addition of the CCA terminus to the 3-prime end of tRNA precursors, and an enzyme that catalyzes the oxidation of a broad range of substrates. Lastly, newly described mutations have informed a whole new dimension on genotype-phenotype relationships. Mutations in the same gene can give rise to a range of phenotypes with a common inflammatory component. This suggests greater than anticipated contributions by modifying alleles and environmental factors to disease expressivity. © Springer-Verlag (outside the USA) 2015.

Manolio T.A.,National Human Genome Research Institute
Nature Reviews Genetics | Year: 2013

Genome-wide association studies (GWASs) have been heralded as a major advance in biomedical discovery, having identified ~2,000 robust associations with complex diseases since 2005. Despite this success, they have met considerable scepticism regarding their clinical applicability; this scepticism arises from such aspects as the modest effect sizes of associated variants and their unclear functional consequences. There are, however, promising examples of GWAS findings that will or that may soon be translated into clinical care. These examples include variants identified through GWASs that provide strongly predictive or prognostic information or that have important pharmacological implications; these examples may illustrate promising approaches to wider clinical application. © 2013 Macmillan Publishers Limited. All rights reserved.

Yang Y.,National Human Genome Research Institute
Cell and Bioscience | Year: 2012

Cell signaling mediated by morphogens is essential to coordinate growth and patterning, two key processes that govern the formation of a complex multi-cellular organism. During growth and patterning, cells are specified by both quantitative and directional information. While quantitative information regulates cell proliferation and differentiation, directional information is conveyed in the form of cell polarities instructed by local and global cues. Major morphogens like Wnts play critical roles in embryonic development and they are also important in maintaining tissue homeostasis. Abnormal regulation of these signaling events leads to a diverse array of devastating diseases including cancer. Wnts transduce their signals through several distinct pathways and they regulate vertebrate embryonic development by providing both quantitative and directional information. Here, taking the developing skeletal system as an example, we review our work on Wnt signaling pathways in various aspects of development. We focus particularly on our most recent findings that showed that in vertebrates, Wnt5a acts as a global cue to establishing planar cell polarity (PCP). Our work suggests that Wnt morphogens regulate development by integrating quantitative and directional information. Our work also provides important insights in disease like Robinow syndrome, brachydactyly type B1 (BDB1) and spina bifida, which can be caused by human mutations in the Wnt/PCP signaling pathway. © 2012 Yang; licensee BioMed Central Ltd.

Ritchie M.D.,Pennsylvania State University | Holzinger E.R.,National Human Genome Research Institute | Li R.,Pennsylvania State University | Pendergrass S.A.,Pennsylvania State University | Kim D.,Pennsylvania State University
Nature Reviews Genetics | Year: 2015

Recent technological advances have expanded the breadth of available omic data, from whole-genome sequencing data, to extensive transcriptomic, methylomic and metabolomic data. A key goal of analyses of these data is the identification of effective models that predict phenotypic traits and outcomes, elucidating important biomarkers and generating important insights into the genetic underpinnings of the heritability of complex traits. There is still a need for powerful and advanced analysis strategies to fully harness the utility of these comprehensive high-throughput data, identifying true associations and reducing the number of false associations. In this Review, we explore the emerging approaches for data integration-including meta-dimensional and multi-staged analyses-which aim to deepen our understanding of the role of genetics and genomics in complex outcomes. With the use and further development of these approaches, an improved understanding of the relationship between genomic variation and human phenotypes may be revealed. © 2014 Macmillan Publishers Limited. All rights reserved.

Schoenebeck J.J.,National Human Genome Research Institute | Ostrander E.A.,National Human Genome Research Institute
Annual review of cell and developmental biology | Year: 2014

Although most modern dog breeds are less than 200 years old, the symbiosis between man and dog is ancient. Since prehistoric times, repeated selection events have transformed the wolf into man's guardians, laborers, athletes, and companions. The rapid transformation from pack predator to loyal companion is a feat that is arguably unique among domesticated animals. How this transformation came to pass remained a biological mystery until recently: Within the past decade, the deployment of genomic approaches to study population structure, detect signatures of selection, and identify genetic variants that underlie canine phenotypes is ushering into focus novel biological mechanisms that make dogs remarkable. Ironically, the very practices responsible for breed formation also spurned morbidity; today, many diseases are correlated with breed identity. In this review, we discuss man's best friend in the context of a genetic model to understand paradigms of heritable phenotypes, both desirable and disadvantageous.

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